Fig. 1. Clinical examination. A large solitary non-healing
ulcer on the right side of the lower lip.
DIFFERENTIAL DIAGNOSIS
Based on history, clinical presentation and location of the lesion
differential diagnoses of long-standing traumatic ulcer, malignancy,
eosinophilic ulcer, tuberculous ulcer, syphilitic ulcer,
herpes-associated erythema multiforme, and deep fungal infection has
been considered.
Single mucosal ulcers may result from direct physical, chemical,
thermal, or even vascular compromise, causing tissue damage and
ulceration. Acute bite injuries are a common example of direct physical
trauma and can be more severe if it occurs when the mucosa is numb after
local anesthesia has been given for a dental procedure. Malocclusion,
aggressive tooth brushing, and self-inflicted damage also cause
traumatic injuries. Inadvertent chewing of electrical wiring may induce
thermal injuries in children. Certain over-the-counter drugs for
treating aphthous ulcers contain high concentrations of silver nitrate,
phenol, or sulfuric acid and can cause solitary ulcerations. Vascular
compromise results in oral ulcerations such as necrotizing
sialometaplasia where there is local infarction of the salivary gland
tissue leading to overwhelming ulceration, exfoliation of the necrotic
tissue, and healing. The most common location for this condition is the
hard palate mucosa although any location that contains minor salivary
glands may be affected1.
Oral ulcerations showing moderately rapid growth rate2and persisting for more than two weeks reflect early signs of
malignancy. The most common malignancy of epithelial origin in the oral
cavity is oral squamous cell carcinoma. Oral squamous cell carcinoma
most commonly affects the floor of the mouth, ventral and lateral
borders of the tongue, and lower lip. It can present as a white, red,
mixed red-white, exophytic or ulcerative lesion. The typical clinical
presentation of oral squamous cell carcinoma is a crater-like solitary
ulcer with indurated rolled border and velvety base3.
Eosinophilic ulceration (Traumatic ulcerative granuloma with stromal
eosinophilia) is a histopathologically distinct variety of chronic
traumatic ulceration of the oral mucosa. It presents with deep
pseudo-invasive inflammatory reactions causing very slow resolution. The
lesion can occur at any age with notably higher occurrence in
males4. Although the anteroventral surface of the
tongue is the most common region for the lesion. It
has also been reported on the gingiva, buccal mucosa, the floor of the
mouth, palate, and lip. Duration of the lesion may vary from 1 week to 8
months5. The ulcerations are indistinguishable from
simple traumatic ulcers; however, occasionally the underlying
granulation tissue can proliferate and make a raised lesion matching the
clinical presentation of lobulated capillary
haemangioma6.
Oral tuberculous lesions are usually secondary to pulmonary tuberculosis
(almost 3% of patients with long-term active tuberculosis) but rarely
primary lesions may occur due to direct inoculation of the microbe into
oral mucosa. Of all the sites involved within the oral cavity, labial
involvement is extremely rare while the tongue is the most common region
affected. An ulceration with undermined edges and a granulating floor is
characteristic of such lesions7.
Primary syphilitic chancres typically present as painless, sometimes
necrotic, ulcers with a rolled border and associated lymphadenopathy.
Common sites of occurrence are the lips, tongue, palate, and nostrils.
The lesions appear within 3 to 90 days of initial inoculation and may
heal spontaneously even without treatment6.
Recurrent Aphthous Major (Sutton’s disease) appears as ulcerations that
are larger than 1 cm in diameter and last for several weeks. The
extremely agonizing condition occurs when major portions of oral mucosa
get covered with extensive ulcerations that coalesce and result in
deeper and bigger lesions. Such conditions interfere with daily
activities like speaking and consuming food. The lesions may sometimes
be wrongly diagnosed as oral squamous cell carcinoma, granulomatous
disease, or a blistering disease such as pemphigus. Slow healing with
scarring causes reduced mobility of the uvula and
tongue6.
Herpes-associated erythema multiforme is an acute disease caused by
herpes simplex virus. It results in exudative dermatic and mucosal
lesions. Oral lesions present as erythematous macules on the lips and
buccal mucosa that undergo epithelial necrosis, bullae formation, and
ulcerations with an irregular margin and strong inflammatory halo.
Bloody encrustations are visible on lips. The lip is the most common
site of preceding herpes simplex virus infection in cases of
herpes-associated erythema multiforme8.
Deep fungal infections (histoplasmosis) are relatively rare in the oral
cavity and most commonly affect immunocompromised patients. Such lesions
typically manifest as chronic mucosal ulcerations or granular soft
tissue overgrowths that arise from either local inoculation or
dissemination by the hematogenous or lymphatic spread. These lesions are
non-specific and can mimic malignancy hence, it is crucial to obtain a
thorough clinical history and an adequate biopsy to confirm the
diagnosis.
Given the potential diagnoses mentioned earlier, it is important to
highlight that lesions of different aetiologies can have the same
clinical features and that histopathologic analysis is crucial for the
final diagnosis, treatment, and management of patients.
DIAGNOSIS AND MANAGEMENT.
Considering the rapid growth of the ulceration and its indurated margins
which provided high suspicion of malignancy we planned to have an
incisional biopsy. However, we decided to seek a second opinion from the
Department of Dermatology where he has been advised the same line of
treatment along with HSV serology and Mantoux test to rule out
hypertrophic herpes simplex and lupus vulgaris respectively.
The patient re-visited us with negative reports for HSV-serology and
Mantoux test. Routine blood investigations were within normal range. An
incisional biopsy was performed with informed consent. The
post-operative healing was uneventful.
The histopathological report illustrated hypertrophied and
hyperkeratinized stratified squamous epithelium with underlying
fibrocollagenous stroma infiltrated by dense mixed inflammatory
infiltrate comprising of predominantly lymphocyte, plasma cells,
neutrophils, and occasional histiocytes admixed with proliferating blood
vessels. There is no evidence of atypia or malignancy (Figure 2).